Synthesis of epothilones, intermediates thereto and analogues thereof

• US 20070032534A1
• Filed: 10/12/2006
• Published: 02/08/2007
• Est. Priority Date: 08/23/2002
• Status: Active Grant

• Current Assignee: Alexey Rivkin, Ana Gabarda, Fumikiko Yoshimura, Huajin Dong, Samuel Danishefsky, Ting-Chao Chou
• Original Assignee: Alexey Rivkin, Ana Gabarda, Fumikiko Yoshimura, Huajin Dong, Samuel Danishefsky, Ting-Chao Chou
• Inventors: Chou, Ting-Chao, Dong, Huajin, Rivkin, Alexey, Danishefsky, Samuel, Yoshimura, Fumikiko, Gabarda, Ana
• Granted Patent: US 7,759,374 B2
• Time in Patent Office: Days
• US Class Current: 514/365
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07D 313/00 Heterocyclic compounds containing rings of more than six members having one oxygen atom as the only ring hetero atom
• CPC Class Codes: C07D 413/06 linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 417/02 containing two hetero rings
• CPC Class Codes: C07D 417/06 linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 493/04 Ortho-condensed systems

Abstract

The present invention provides compounds of formula (I): as described generally and in classes and subclasses herein. The present invention additionally provides pharmaceutical compositions comprising compounds of formula (I) and provides methods of treating cancer comprising administering a compound of formula (I).

Claims

1. A compound of the formula:

45. A pharmaceutical composition for the treatment of cancer comprising a compound of claim 1 and a pharmaceutically acceptable excipient.

46. The pharmaceutical composition of claim 45 further comprising Cremophor.

47. The pharmaceutical composition of claim 45 further comprising Cremophor and ethanol.

48. The pharmaceutical composition of claim 45, wherein the compound is suspended in 1:

1 Cremophor/EtOH.

49. The pharmaceutical composition of claim 45 further comprising an additional cytotoxic agent.

50. A pharmaceutical composition for the treatment of cancer comprising:

a therapeutically effective amount of a compound of claim 1, or pharmaceutically acceptable salts thereof; and

a pharmaceutically acceptable carrier or diluent,

wherein the therapeutically effective amount of the compound is an amount sufficient to deliver about 0.001 to about 40 mg compound per kg body weight of a subject.

51. A method of treating cancer comprising:

administering a therapeutically effective amount of a compound of claim 1 to a subject in need thereof.

52. The method of claim 51, wherein the therapeutically effective amount of the compound is an amount sufficient to deliver about 0.001 mg to about 40 mg compound per kg body weight.

53. The method of claim 51, wherein the therapeutically effective amount of the compound is an amount sufficient to deliver about 0.1 mg to about 25 mg compound per kg body weight.

2. A compound of the formula:

3. The compound of claim 2 wherein R_B is methyl.

4. The compound of claim 2 wherein R_B is —

CF₃.

5. The compound of claim 2, wherein R₈ is methyl.

8. The compound of claim 2, wherein R₈ is —

CH₂OH.

9. The compound of claim 2, wherein R₈ is —

CH₂NH₂.

10-44. -44. (canceled)

54-117. -117. (canceled)